title: Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC.
abstract: This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.
authors.affiliation: Antibiotics Department, Pernambuco Federal University, 50670-901 Recife-PE, Brazil. Electronic address: flavia_19lucena@yahoo.com.br.
authors.forename: Flávia Raquel Santos
authors.initials: FR
authors.lastname: Lucena
authors.forename: Larissa C C
authors.initials: LC
authors.lastname: de Araújo
authors.forename: Maria do D
authors.initials: Mdo D
authors.lastname: Rodrigues
authors.forename: Teresinha G
authors.initials: TG
authors.lastname: da Silva
authors.forename: Valéria R A
authors.initials: VR
authors.lastname: Pereira
authors.forename: Gardênia C G
authors.initials: GC
authors.lastname: Militão
authors.forename: Danilo A F
authors.initials: DA
authors.lastname: Fontes
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Rolim-Neto
authors.forename: Fausthon F
authors.initials: FF
authors.lastname: da Silva
authors.forename: Silene C
authors.initials: SC
authors.lastname: Nascimento
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry*; D014233:Tricarboxylic Acids / Q000737:chemistry*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009942:Organometallic Compounds; D014233:Tricarboxylic Acids; D003300:Copper; C069849:trimesic acid; D005472:Fluorouracil
keywords: 5-fluorouracil; Anti-inflammatory and cytotoxic activities; Apoptosis; Cu-BTC MOF; Slow release